Trial Outcomes & Findings for A Study of the Combination of Necitumumab (LY3012211) and Pembrolizumab (MK3475) in Participants With NSCLC (NCT NCT02451930)

NCT ID: NCT02451930

Last Updated: 2020-10-05

Results Overview

A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: Grade 3 or 4 nonhematologic toxicity, Grade 4 nausea, vomiting, or diarrhea that persists more than 3 days despite maximal supportive intervention, Grade 3 thrombocytopenia with bleeding requiring transfusion, Grade 4 thrombocytopenia with or without bleeding, Grade 4 neutropenia that persists more than 5 days, Grade 3 or 4 neutropenia with fever, Grade ≥3 skin toxicity despite best supportive care with some exceptions, if a total at least 75% of the planned dose for both agents cannot be administered in the first cycle due to toxicity, prolonged delay (\>2 weeks) in initiating cycle 2 due to treatment-related toxicity and Grade 5 toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 71 participants
• Primary outcome timeframe: Baseline through Cycle 1 (21 day cycles)
• Results posted on: 2020-10-05

Participant Flow

Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

Participant milestones

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2, Part B and Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in Part A cohort 2 participants with any histology, Part B and C participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.
Overall Study STARTED	3	68
Overall Study Received at Least One Dose of Study Drug	3	68
Overall Study Part A Cohort 2 Participants	0	6
Overall Study Part B Participants	0	55
Overall Study Part C Participants	0	7
Overall Study COMPLETED	1	38
Overall Study NOT COMPLETED	2	30

Reasons for withdrawal

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2, Part B and Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in Part A cohort 2 participants with any histology, Part B and C participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.
Overall Study Death	0	15
Overall Study Lost to Follow-up	0	3
Overall Study Sponsor Decision	2	10
Overall Study Withdrawal by Subject	0	1
Overall Study Other	0	1

Baseline Characteristics

A Study of the Combination of Necitumumab (LY3012211) and Pembrolizumab (MK3475) in Participants With NSCLC

Baseline characteristics by cohort

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2 and Part B: 800 mg Neci + 200 mg Pembro n=61 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology.	Part C: 800 mg Neci + 200 mg Pembro n=7 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Total n=71 Participants Total of all reporting groups
Age, Continuous Part A and B	67.0 years STANDARD_DEVIATION 7.21 • n=5 Participants	63.13 years STANDARD_DEVIATION 9.82 • n=7 Participants	NA years STANDARD_DEVIATION NA • n=5 Participants	63.31 years STANDARD_DEVIATION 9.73 • n=4 Participants
Age, Continuous Part C	NA years STANDARD_DEVIATION NA • n=5 Participants	NA years STANDARD_DEVIATION NA • n=7 Participants	64.14 years STANDARD_DEVIATION 8.55 • n=5 Participants	64.14 years STANDARD_DEVIATION 8.55 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	17 Participants n=7 Participants	2 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	44 Participants n=7 Participants	5 Participants n=5 Participants	51 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	21 Participants n=7 Participants	0 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	39 Participants n=7 Participants	7 Participants n=5 Participants	48 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	47 Participants n=7 Participants	0 Participants n=5 Participants	50 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	13 Participants n=7 Participants	0 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment United States	0 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Japan	0 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment France	2 Participants n=5 Participants	40 Participants n=7 Participants	0 Participants n=5 Participants	42 Participants n=4 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	14 Participants n=7 Participants	0 Participants n=5 Participants	15 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline through Cycle 1 (21 day cycles)

Population: All participants who received at least one dose of study drug in Part A and Part C.

A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: Grade 3 or 4 nonhematologic toxicity, Grade 4 nausea, vomiting, or diarrhea that persists more than 3 days despite maximal supportive intervention, Grade 3 thrombocytopenia with bleeding requiring transfusion, Grade 4 thrombocytopenia with or without bleeding, Grade 4 neutropenia that persists more than 5 days, Grade 3 or 4 neutropenia with fever, Grade ≥3 skin toxicity despite best supportive care with some exceptions, if a total at least 75% of the planned dose for both agents cannot be administered in the first cycle due to toxicity, prolonged delay (>2 weeks) in initiating cycle 2 due to treatment-related toxicity and Grade 5 toxicity.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro n=6 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro n=7 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months)

Population: All participants who received at least one dose of study drug in Part A and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro n=61 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A and Part B	66.7 Percentage of Participants Interval 9.4 to 99.2	21.3 Percentage of Participants Interval 11.9 to 33.7	—	—

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 40 Months)

Population: All participants who received at least one dose of study drug in Part A Cohort 2, Part B and Part C. Part C were Japan participants. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=68 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A Cohort 2, Part B and Part C	25.0 percentage of participants Interval 15.3 to 37.0	—	—	—

SECONDARY outcome

Timeframe: Predose sample (within 1 hour before infusion) and postdose sample (within 10 min after infusion) on Day 1 at Cycles 1, 2, 4, 6, 8; 30 days post treatment discontinuation

Population: All participants who received at least one dose of study drug and had evaluable PK data in Part A, Part B and Part C.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro n=6 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro n=44 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro n=7 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C Pre-Dose Cycle 2	50.4 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 54.7	70 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 49.7	58.2 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 56	90.4 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 18.4
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C Pre-Dose Cycle 4	79.2 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 32.5	148 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 32.1	101 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 48	136 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 9.51
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C Pre-Dose Cycle 6	89.5 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 24.7	195 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 12.2	114 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 58.3	114 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 66.5
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C Pre-Dose Cycle 8	98.5 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 3.73	155 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 33	91 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 62.7	209 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 18.7
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C End-of-Infusion Cycle 1	152 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 32.1	269 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 15.6	226 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 24.6	281 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 26
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C End-of-Infusion Cycle 2	194 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 29	352 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 25.3	273 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 36.8	391 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 25.4
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C End-of-Infusion Cycle 4	246 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 28.7	353 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 45.3	315 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 45.4	428 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 5.18
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C End-of-Infusion Cycle 6	234 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 26.3	396 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 8.53	312 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 42.1	406 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 12.9
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C End-of-Infusion Cycle 8	291 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 20.8	526 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 8.49	295 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 46.4	507 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 7.95

SECONDARY outcome

Timeframe: Predose Cycle 1 Day 1 through Predose Cycle 8 Day 1 (21 Day Cycles)

Population: All participants who received at least one dose of study drug who had evaluable data in Part A, Part B and Part C.

Result is considered as treatment emergent anti-necitumumab antibody positive if postbaseline titer = 4*baseline titer for baseline titer > 0 or if postbaseline titer >= 20 for samples with antibody not detected.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro n=61 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro n=7 Participants Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C	0 Participants	2 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months)

Population: All participants who received at least one dose of study drug in Part A Cohort 2 and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=61 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) in Part A Cohort 2 and Part B	62.3 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 16 Months)

Population: All participants who received at least one dose of study drug who had evaluable data in Part A Cohort 2 and Part B. 11 participants were censored. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

DOR was defined only for responders (participants with confirmed CR or PR). It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever was earlier.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=4 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Duration of Response (DoR) in Part A Cohort 2 and Part B	10.94 months Interval 4.17 to Upper confidence interval was not evaluable due to high censoring.	—	—	—

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up To 16 Months)

Population: All participants who received at least one dose of study drug and who had evaluable data in Part A Cohort 2 and Part B. 21 participants were censored. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

PFS was defined as the time from the date of first dose of study drug until first observation of objective (radiographically documented) PD as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=40 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Progression Free Survival (PFS) in Part A Cohort 2 and Part B	3.98 Months Interval 2.23 to 6.87	—	—	—

SECONDARY outcome

Timeframe: Baseline to Death from Any Cause (Up To 16 Months)

Population: All participants who received at least one dose of study drug in Part A Cohort 2 and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

OS duration was measured from the date of first dose of study drug (necitumumab and/or pembrolizumab) to the date of death from any cause.

Outcome measures

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=61 Participants Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japan participants.	Part C: 800mg Neci + 200mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. Part C were Japanese participants.
Overall Survival (OS) in Part A Cohort 2, Part B	NA months OS was not reached because data were not mature at data cutoff.	—	—	—

Adverse Events

Part A Cohort 1: 600 mg Neci + 200 mg Pembro

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A Cohort 2, Part B and Part C: 800mg Neci + 200mg Pembro

Serious events: 30 serious events

Other events: 66 other events

Deaths: 23 deaths

Serious adverse events

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 participants at risk Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2, Part B and Part C: 800mg Neci + 200mg Pembro n=68 participants at risk Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in Part B and C participants with Stage IV NSCLC of squamous and nonsquamous histology and Part A cohort 2 participants with any histology. Part C were Japan participants.
Cardiac disorders Cardiac arrest	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Cardiac disorders Cardiac failure congestive	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Cardiac disorders Pericarditis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Cardiac disorders Ventricular extrasystoles	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Endocrine disorders Hyperthyroidism	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Pancreatitis acute	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	0.00% 0/68 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Asthenia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Pain	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Hepatobiliary disorders Biliary tract disorder	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Enterococcal sepsis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Folliculitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Pneumonia bacterial	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Respiratory tract infection	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Urinary tract infection	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Urosepsis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Aphasia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Encephalopathy	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Ischaemic stroke	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Seizure	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Psychiatric disorders Confusional state	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Hypersensitivity pneumonitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	4.4% 3/68 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Fixed eruption	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Vascular disorders Orthostatic hypotension	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Vascular disorders Venous thrombosis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

Other adverse events

Measure	Part A Cohort 1: 600 mg Neci + 200 mg Pembro n=3 participants at risk Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies).	Part A Cohort 2, Part B and Part C: 800mg Neci + 200mg Pembro n=68 participants at risk Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in Part B and C participants with Stage IV NSCLC of squamous and nonsquamous histology and Part A cohort 2 participants with any histology. Part C were Japan participants.
Endocrine disorders Hypothyroidism	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 7 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Eye disorders Dry eye	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Constipation	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	16.2% 11/68 • Number of events 16 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	23.5% 16/68 • Number of events 23 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 13 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Pancreatitis acute	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	0.00% 0/68 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Stomatitis	66.7% 2/3 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	23.5% 16/68 • Number of events 26 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	14.7% 10/68 • Number of events 17 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Asthenia	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	32.4% 22/68 • Number of events 46 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Chills	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Fatigue	33.3% 1/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	30.9% 21/68 • Number of events 29 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Non-cardiac chest pain	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 6 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	13.2% 9/68 • Number of events 21 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Skin infection	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 11 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
General disorders Xerosis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	11.8% 8/68 • Number of events 28 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Bronchitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Conjunctivitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	11.8% 8/68 • Number of events 10 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Folliculitis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 10 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Paronychia	66.7% 2/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	14.7% 10/68 • Number of events 18 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Pharyngitis	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Infections and infestations Respiratory tract infection	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	16.2% 11/68 • Number of events 17 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Amylase increased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 19 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	14.7% 10/68 • Number of events 21 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 9 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Blood creatine phosphokinase increased	33.3% 1/3 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	8.8% 6/68 • Number of events 7 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations International normalised ratio increased	33.3% 1/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Lipase increased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 22 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Investigations Weight decreased	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 8 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	29.4% 20/68 • Number of events 26 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	7.4% 5/68 • Number of events 14 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Hypocalcaemia	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 13 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Hypomagnesaemia	66.7% 2/3 • Number of events 12 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	35.3% 24/68 • Number of events 62 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Metabolism and nutrition disorders Hypophosphataemia	33.3% 1/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	13.2% 9/68 • Number of events 22 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 2/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	17.6% 12/68 • Number of events 14 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 7 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Dizziness	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	11.8% 8/68 • Number of events 8 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Dysgeusia	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	2.9% 2/68 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	20.6% 14/68 • Number of events 16 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Nervous system disorders Paraesthesia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 6 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Psychiatric disorders Insomnia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 11 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Renal and urinary disorders Haematuria	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	4.4% 3/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Renal and urinary disorders Proteinuria	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Reproductive system and breast disorders Menorrhagia	0.00% 0/1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.3% 1/19 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	16.2% 11/68 • Number of events 20 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 5 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	17.6% 12/68 • Number of events 17 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Dermatitis acneiform	100.0% 3/3 • Number of events 7 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	67.6% 46/68 • Number of events 96 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Dry skin	66.7% 2/3 • Number of events 2 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	38.2% 26/68 • Number of events 36 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Hirsutism	0.00% 0/1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.5% 2/19 • Number of events 4 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	22.1% 15/68 • Number of events 36 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	5.9% 4/68 • Number of events 15 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	16.2% 11/68 • Number of events 33 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Skin and subcutaneous tissue disorders Skin ulcer	33.3% 1/3 • Number of events 3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	1.5% 1/68 • Number of events 1 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.	10.3% 7/68 • Number of events 11 • Baseline Up to 49 Months All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At risk adjusted accordingly. Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60